The major objective of the proposed research is the further development of practical techniques for mass spectrometric analysis of nonvolatile organic molecules adsorbed on solid surfaces. The approach involves direct production of ions from the condensed phase by either pulsed laser desorption or keV particle impact. Since production of neutral gas phase molecules as intermediates is not required, these techniques are applicable to many nonvolatile and thermally labile molecules not amenable to conventional mass spectrometric analysis. These desorption-ionization techniques are combined with "thermospray" sample deposition on a moving belt transport system to provide a new on-line LC-MS apparatus which is applicable to nonvolatile samples. The feasibility of using these new desorption-ionization methods for direct mass spectrometric analysis of samples on TLC plates is also being explored. In the proposed continuation of this research, initial attention will focus on completing the development of practical on-line LC-MS systems using both pulsed laser and keV particle desorption. A new time-of-flight mass analyzer will be developed and constructed which should allow the full potential of the laser desorption techniques to be realized. Considerable effort will be expanded on attempting to optimize the performance of both desorption techniques and the performance of the "optimized" systems for LC-MS analysis of a wide range of biologically interesting molecules will be determined. The utility of these techniques will be evaluated by comparing their performance with that obtained by competitive LC-MS approaches such as direct thermospray mass spectrometry.